ArticleThe American journal of pathology2007
Classic interleukin-6 receptor signaling and interleukin-6 trans-signaling differentially control angiotensin II-dependent hypertension, cardiac signal transducer and activator of transcription-3 activation, and vascular hypertrophy in vivo.
Article in The American journal of pathology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 127 citations in OpenAlex.
- Refining therapeutic targeting of interleukin-6 by signalling mode selectivity.Nature reviews. Drug discovery · 2026Review
- Suppression of Post-Ischemic Cardiac Remodelling and Inflammatory Response by a Novel Sphingolipid Modifier, CIN038.International journal of molecular sciences · 2026Article
- Immune and inflammatory mechanisms in hypertension.Nature reviews. Cardiology · 2024Review
- The Role of Pro-Inflammatory Cytokines in the Pathogenesis of Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Extracellular vesicular microRNAs and cardiac hypertrophy.Frontiers in endocrinology · 2024Review
- A new immune disease: systemic hypertension.Clinical kidney journal · 2023Review
- Novel Biomarkers for Atherosclerotic Disease: Advances in Cardiovascular Risk Assessment.Life (Basel, Switzerland) · 2023Review
- Signaling through the IL-6-STAT3 Pathway Promotes Proteolytically-Active Macrophage Accumulation Necessary for Development of Small AAA.Vascular and endovascular surgery · 2023Article
- The Cardiomyocyte in Heart Failure with Preserved Ejection Fraction-Victim of Its Environment?Cells · 2022Review
- GJD Modulates Cardiac/Vascular Inflammation and Decreases Blood Pressure in Hypertensive Rats.Mediators of inflammation · 2022Article
- Harmine is an effective therapeutic small molecule for the treatment of cardiac hypertrophy.Acta pharmacologica Sinica · 2022Article
- Comorbidities and inflammation associated with ovarian cancer and its influence on SARS-CoV-2 infection.Journal of ovarian research · 2021Review
- Loganin Inhibits Angiotensin II-Induced Cardiac Hypertrophy Through the JAK2/STAT3 and NF-κB Signaling Pathways.Frontiers in pharmacology · 2021Article
- Inflammatory Cytokines, Immune Cells, and Organ Interactions in Heart Failure.Frontiers in physiology · 2021Review
- Supplemental 25-hydroxycholecalciferol Alleviates Inflammation and Cardiac Fibrosis in Hens.International journal of molecular sciences · 2020Article
- The E3 ubiquitin ligase HectD3 attenuates cardiac hypertrophy and inflammation in mice.Communications biology · 2020Article
- Inhibition of Interleukin-6/glycoprotein 130 signalling by Bazedoxifene ameliorates cardiac remodelling in pressure overload mice.Journal of cellular and molecular medicine · 2020Article
- Bioactive peptides attenuate cardiac hypertrophy and fibrosis in spontaneously hypertensive rat hearts.Journal of food and drug analysis · 2020Article
- Inhibition of the ROS-EGFR Pathway Mediates the Protective Action of Nox1/4 Inhibitor GKT137831 against Hypertensive Cardiac Hypertrophy via Suppressing Cardiac Inflammation and Activation of Akt and ERK1/2.Mediators of inflammation · 2020Article
- Soluble interleukin-6 receptor in young adults and its relationship with body composition and autonomic nervous system.Physiological reports · 2019Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Interleukin (IL)-6 acts via a receptor complex consisting of the cognate IL-6 receptor (IL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130). Here, we investigated the role of these IL-6R components in hypertension and vascular hypertrophy in mice. Angiotensin (Ang) II (1.1 mg/kg/day) caused hypertension and cardiac/aortic hypertrophy in wild-type, but not IL-6(-/-), mice throughout 7 days. A recombinant dimeric soluble gp130 (sgp130Fc; 50 to 100 microg, i.p.) blocked Ang II hypertension but not hypertrophy in wild-type mice. Cognate IL-6R was detected in aortic smooth muscle, but its levels and those of plasma sIL-6R were approximately 50% decreased in IL-6(-/-) mice. Ang II infusion activated signal transducer and activator of transcription-3 in heart of WT and decreased Ang II receptor 1 (ATR1) expression in aorta. Both responses were unaffected by sgp130Fc and absent in IL-6(-/-) mice. In summary, we show that IL-6 trans-signaling is required for Ang II-dependent hypertension, but that hypertrophy, down-regulation of AT1R, and cardiac signal transducer and activator of transcription-3 activation are mediated via cognate IL-6R. These data show that IL-6 responses in a single disease context are governed by both modes of IL-6 signaling, with each pathway eliciting different outcomes. Inhibition of IL-6 signaling is suggested as a potential therapy for hypertension and cardiac hypertrophy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.